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DC Vaccine Combined With IL-2 and IFNα-2a in Treating Patients With mRCC

Primary Purpose

Kidney Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Aldesleukin,
autologous tumor cell vaccine
recombinant interferon alfa
Sponsored by
Dartmouth-Hitchcock Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Cancer focused on measuring recurrent renal cell cancer, stage IV renal cell cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologically confirmed metastatic renal cell carcinoma with measurable disease. Tumor tissue available and properly stored for lysate preparation. Patients must be at least 4 weeks from their last immunotherapy, radiation, surgery or chemotherapy (6 weeks for nitrosureas) and recovered from all ill effects. Karnofsky Performance Status ≥60% Life expectancy ≥ twelve weeks Adequate end organ function: Hematological: ANC ≥ 1000cells/μL, platelets ≥ 75,000/μL, hemoglobin ≥ 8.5 g/dl Liver: AST < 2 x ULN (upper limit of normal) unless due to metastases then < 5 x ULN, serum total bilirubin < 2 x ULN (except for patients with Gilbert's Syndrome) Renal: serum creatinine < 2.0 x ULN. Pulmonary: FEV1 > 2.0 liters or > 75% of predicted for height and age. Cardiac: No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than 6 months prior to entry, or serious cardiac arrhythmias. Patients over 40 or have had previous myocardial infarction greater than 6 months prior to entry will be required to have a negative or low probability cardiac stress test for cardiac ischemia. CNS: No history of brain metastases. Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study. Appropriate Contraception in both sexes EXCLUSION CRITERIA: Patients may have not have been treated previously with IL-2, IFNα or autologous vaccine. Concomitant second malignancy except for non-melanoma skin cancer, and non- invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence, breast CIS. In patients with a prior history of invasive malignancy, less than five years in complete remission Positive serology for HIV, hepatitis B or hepatitis C, Significant co-morbid illness such as uncontrolled diabetes or active infection that would preclude treatment on this regimen. Use of corticosteroids or other immunosuppression (if patient had been taking steroids, at least 4 weeks must have passed since the last dose). History of autoimmune disease.

Sites / Locations

  • Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vaccine, Aldesleukin-2, Interferon-a

Arm Description

All patients will be treated with autologous tumor cell vaccine administered into inguinal lymph nodes via ultrasound guidance in addition to systemic IL-2 and recombinant interferon alfa. Two cycles of induction IL-2/IFNα-2a followed by 3 cycles of maintenance IL-2 + IFNα-2a.

Outcomes

Primary Outcome Measures

Clinical Response as Measured by RECIST
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

Immunity as Measured by T-cell and Antibody Responses to the Tumor
All patients receiving at least one week of treatment and have at least two time points available for assessment of immune parameters will be include in the evaluation of immune status.

Full Information

First Posted
June 10, 2004
Last Updated
May 29, 2018
Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00085436
Brief Title
DC Vaccine Combined With IL-2 and IFNα-2a in Treating Patients With mRCC
Official Title
A Phase II Study Of Autologous Tumor/DC Vaccine (DC Vaccine) Combined With Interleukin-2 (IL-2) And Interferon-α-2a (IFNα-2a) In Patients With Metastatic Renal Cell Carcinoma (RCC)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dartmouth-Hitchcock Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Vaccines made from a patient's dendritic cells and tumor cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's lymphocytes to kill kidney cancer cells. Interferon alfa may interfere with the growth of cancer cells. Combining vaccine therapy with interleukin-2 and interferon alfa may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving vaccine therapy together with interleukin-2 and interferon alfa works in treating patients with metastatic renal cell carcinoma (kidney cancer).
Detailed Description
OBJECTIVES: Primary Determine the clinical response rate in patients with metastatic renal cell carcinoma treated with autologous dendritic cells (DC) loaded with autologous tumor lysate (DC vaccine) in combination with interleukin-2 and interferon-alfa. Determine the toxicity of this regimen in these patients. Secondary Determine, within relevant immune pathways, the treatment-related, tumor-specific immune response in patients treated with this regimen. Correlate tumor-specific immune response with objective clinical response in patients treated with this regimen. OUTLINE: Induction therapy: Patients undergo leukapheresis on day -9. Patients receive autologous dendritic cells (DC) loaded with autologous tumor lysate (DC vaccine) by intranodal injection on days 0 and 14; interleukin-2 (IL-2) IV continuously on days 1-5 and 15-19; and interferon-alfa (IFN-α) subcutaneously (SC) once daily on days 1, 3, 5, 15, 17, and 19. Maintenance therapy: Patients undergo leukapheresis on days 33, 61, and 89. Patients receive DC vaccine by intranodal injection on days 42, 70, and 98; IL-2 IV continuously on days 43-47, 71-75, and 99-103; and IFN-α SC once daily on days 43, 45, 47, 71, 73, 75, 99, 101, and 103. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 18-33 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Cancer
Keywords
recurrent renal cell cancer, stage IV renal cell cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vaccine, Aldesleukin-2, Interferon-a
Arm Type
Experimental
Arm Description
All patients will be treated with autologous tumor cell vaccine administered into inguinal lymph nodes via ultrasound guidance in addition to systemic IL-2 and recombinant interferon alfa. Two cycles of induction IL-2/IFNα-2a followed by 3 cycles of maintenance IL-2 + IFNα-2a.
Intervention Type
Biological
Intervention Name(s)
Aldesleukin,
Other Intervention Name(s)
IL-2 (Proleukin®, Chiron)
Intervention Description
Recombinant human interleukin-2 (Proleukin, Chiron Therapeutics) will be administered as a five day (120 hr) continuous intravenous infusion at a dose of 18x106 IU per square meter of body surface area per day as per the Negrier regimen (21). The treatment schedule consists of two induction cycles and three maintenance cycles. Each induction cycle consists of two five-day courses of interleukin-2 infusion separated by a nine-day break. Each maintenance cycle consists of a five-day infusion followed by 23-day rest period of no therapy.
Intervention Type
Biological
Intervention Name(s)
autologous tumor cell vaccine
Other Intervention Name(s)
DC Vaccine
Intervention Description
we will administer 1 X 107 DC cells. The autologous tumor cell vaccine (1 X 107 cells/1cc) in lactated ringers solution and injected into one (or two if clinically necessary) inguinal lymph nodes under ultrasound guidance. Each cycle of DC vaccine will be administered alternately in the right and left inguinal lymph nodes.
Intervention Type
Biological
Intervention Name(s)
recombinant interferon alfa
Other Intervention Name(s)
interferon alfa-2a; Roferon
Intervention Description
Recombinant human interferon alfa-2a (Roferon, Roche), at a dose of 6 million IU per day three times a week subcutaneously will be given during the two interleukin-2 induction cycles and during each interleukin-2 maintenance cycle
Primary Outcome Measure Information:
Title
Clinical Response as Measured by RECIST
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame
monthly, then every 2-3 months
Secondary Outcome Measure Information:
Title
Immunity as Measured by T-cell and Antibody Responses to the Tumor
Description
All patients receiving at least one week of treatment and have at least two time points available for assessment of immune parameters will be include in the evaluation of immune status.
Time Frame
monthly for 5 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed metastatic renal cell carcinoma with measurable disease. Tumor tissue available and properly stored for lysate preparation. Patients must be at least 4 weeks from their last immunotherapy, radiation, surgery or chemotherapy (6 weeks for nitrosureas) and recovered from all ill effects. Karnofsky Performance Status ≥60% Life expectancy ≥ twelve weeks Adequate end organ function: Hematological: ANC ≥ 1000cells/μL, platelets ≥ 75,000/μL, hemoglobin ≥ 8.5 g/dl Liver: AST < 2 x ULN (upper limit of normal) unless due to metastases then < 5 x ULN, serum total bilirubin < 2 x ULN (except for patients with Gilbert's Syndrome) Renal: serum creatinine < 2.0 x ULN. Pulmonary: FEV1 > 2.0 liters or > 75% of predicted for height and age. Cardiac: No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than 6 months prior to entry, or serious cardiac arrhythmias. Patients over 40 or have had previous myocardial infarction greater than 6 months prior to entry will be required to have a negative or low probability cardiac stress test for cardiac ischemia. CNS: No history of brain metastases. Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study. Appropriate Contraception in both sexes EXCLUSION CRITERIA: Patients may have not have been treated previously with IL-2, IFNα or autologous vaccine. Concomitant second malignancy except for non-melanoma skin cancer, and non- invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence, breast CIS. In patients with a prior history of invasive malignancy, less than five years in complete remission Positive serology for HIV, hepatitis B or hepatitis C, Significant co-morbid illness such as uncontrolled diabetes or active infection that would preclude treatment on this regimen. Use of corticosteroids or other immunosuppression (if patient had been taking steroids, at least 4 weeks must have passed since the last dose). History of autoimmune disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc S. Ernstoff, MD
Organizational Affiliation
Norris Cotton Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756-0002
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19622576
Citation
Schwaab T, Schwarzer A, Wolf B, Crocenzi TS, Seigne JD, Crosby NA, Cole BF, Fisher JL, Uhlenhake JC, Mellinger D, Foster C, Szczepiorkowski ZM, Webber SM, Schned AR, Harris RD, Barth RJ Jr, Heaney JA, Noelle RJ, Ernstoff MS. Clinical and immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with Aldesleukin (Interleukin 2) and IFN-alpha2a therapy in metastatic renal cell carcinoma patients. Clin Cancer Res. 2009 Aug 1;15(15):4986-92. doi: 10.1158/1078-0432.CCR-08-3240. Epub 2009 Jul 21.
Results Reference
result

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DC Vaccine Combined With IL-2 and IFNα-2a in Treating Patients With mRCC

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